Prenatal treatment of ornithine transcarbamylase deficiency.

PURPOSE OF STUDY: Patients with neonatal urea cycle defects (UCDs) typically experience severe hyperammonemia during the first days of life, which results in serious neurological injury or death. Long-term prognosis despite optimal pharmacological and dietary therapy is still poor. The combination of intravenous sodium phenylacetate and sodium benzoate (Ammonul®) can eliminate nitrogen waste independent of the urea cycle. We report attempts to improve outcomes for males with severe ornithine transcarbamylase deficiency (OTCD), a severe X-linked condition, via prenatal intravenous administration of Ammonul and arginine to heterozygous carrier females of OTCD during labor. METHODS USED: Two heterozygote OTCD mothers carrying male fetuses with a prenatal diagnosis of OTCD received intravenous Ammonul, arginine and dextrose-containing fluids shortly before birth. Maintenance Ammonul and arginine infusions and high-caloric enteral nutrition were started immediately after birth. Ammonul metabolites were measured in umbilical cord blood and the blood of the newborn immediately after delivery. Serial ammonia and biochemical analyses were performed following delivery. SUMMARY OF RESULTS: Therapeutic concentrations of Ammonul metabolites were detected in umbilical cord and neonatal blood samples. Plasma ammonia and glutamine levels in the postnatal period were within the normal range. Peak ammonia levels in the first 24-48h were 53mcmol/l and 62mcmol/l respectively. The boys did not experience neurological sequelae secondary to hyperammonemia and received liver transplantation at ages 3months and 5months. The patients show normal development at ages 7 and 3years. CONCLUSION: Prenatal treatment of mothers who harbor severe OTCD mutations and carry affected male fetuses with intravenous Ammonul and arginine, followed by immediate institution of maintenance infusions after delivery, results in therapeutic levels of benzoate and phenylacetate in the newborn at delivery and, in conjunction with high-caloric enteral nutrition, prevents acute hyperammonemia and neurological decompensation. Following initial medical management, early liver transplantation may improve developmental outcome.

Sudden onset vision loss in an 8-year-old female with McCune-Albright syndrome.

We describe a case of an 8-year-old girl with large irregular café au lait macules on the right cheek and right lower extremity presenting with sudden onset vision loss and found to have polyostotic fibrous dysplasia on imaging. The classic triad of McCune-Albright syndrome is discussed along with the importance of recognition in patients with partial presentation. This case also highlights a rare and potentially devastating neurologic complication of McCune-Albright syndrome, as well as the need for early diagnosis and continual surveillance in these patients.

Ocular features of NGLY1 deficiency from a prospective longitudinal cohort.

BACKGROUND: NGLY1 deficiency is a rare autosomal recessive disorder with core features of global developmental delay, liver enzyme abnormalities, movement disorder, polyneuropathy, and hypo- or alacrima. We characterized the full spectrum and evolution of the ocular phenotype in a prospective natural history of NGLY1 deficiency. METHODS: We collected ophthalmological data on 29 individuals with NGLY1 deficiency in a natural history study. Medical records were reviewed to confirm caregiver-reported symptoms. Of the 29, 15 participants appeared for at least one ophthalmological examination. RESULTS: Caregivers reported at least one ocular sign or symptom in 90% of participants (26/29), most commonly decreased tears, refractive error, and chronic infection. Daily eye medication, including artificial tears, ophthalmic ointment, and topical antibiotics were used by 62%. Ophthalmological examination confirmed refractive errors in 93% (14/15) and corneal abnormalities in 73% (11/15). CONCLUSIONS: Given nearly universal hypolacrima and additional prominent ocular findings in NGLY1 deficiency, a targeted ocular history and ophthalmologic examination may facilitate prompt diagnosis and early initiation of preventive eye care, preserving vision and overall ocular health.

Referral patterns for infantile cataracts in two regions of the United States.

BACKGROUND: Delayed treatment of congenital or infantile cataracts can cause deprivation amblyopia. Prompt diagnosis and surgical intervention is critical for optimal outcomes. This study assessed referral patterns for congenital or infantile cataracts in two regions of the United States. METHODS: The medical records of children 0-1 years of age with congenital or infantile cataracts at Stanford University (2008-2018) and Emory University (2010-2015) were reviewed retrospectively. RESULTS: A total of 111 children were included. Of these, 82 (74%) were initially evaluated by a primary care doctor, of whom 40 (49%) were referred directly to a pediatric cataract surgeon. Of 61 newborns 0-2 months of age, 9 (15%) were initially referred to an eye care provider before 6 weeks of age, but the initial evaluation by a pediatric cataract surgeon was delayed until after 6 weeks of age. Referral patterns were similar between the two institutions (P = 0.06). CONCLUSIONS: Many children with congenital of infantile cataracts are initially referred by a primary care doctor to an eye care provider who does not perform pediatric cataract surgery. Nevertheless, the majority of newborn infants with cataracts were evaluated by a pediatric cataract surgeon before 6 weeks of age.

Orbital recurrence of B-progenitor acute lymphoblastic leukemia in a child.

Orbital mass is an exceedingly rare presentation of acute lymphoblastic leukemia. This report describes a 12-year-old boy with recurrent orbital pre-B-cell acute lymphoblastic leukemia and reviews the literature on the incidence, presentation, prognosis, and management of orbital tumors in acute lymphoblastic leukemia. Early diagnosis and treatment of orbital acute lymphoblastic leukemia with a multidisciplinary approach is essential to minimize or prevent deterioration of vision and optimize clinical outcomes.

Survey of practice patterns for the management of ophthalmic genetic disorders among AAPOS members: report by the AAPOS Genetic Eye Disease Task Force.

To better understand AAPOS member pediatric ophthalmologists' knowledge and needs regarding genetic eye disorders, the AAPOS Genetic Eye Disease Task Force developed a 16-question survey that was circulated to national and international AAPOS members. Responses to questions on practice patterns, baseline knowledge, and educational interests regarding patients with suspected ophthalmic genetic disorders were collected. A majority of respondents (93%) evaluate patients with suspected genetic disorders. Knowledge gaps were present in heritability of certain conditions, genetic testing strategies, and referral to clinical trials. Most respondents expressed interest in further education in these areas. A model for care is proposed as a first step in the education process.

Sclerocornea associated with the chromosome 22q11.2 deletion syndrome.

Reported ocular findings in the 22q11.2 deletion syndrome (which encompasses the phenotypes of DiGeorge, velocardiofacial, and Takao (conotruncal-anomaly-face) syndromes) have included posterior embryotoxon (prominent, anteriorly displaced Schwalbe's line at the corneal limbus or edge), retinal vascular tortuosity, eyelid hooding, strabismus, and astigmatism. We present seven 22q11.2 patients from multiple centers with sclerocornea, an eye finding previously unreported in the literature. Four boys and three girls were identified with sclerocornea, systemic DGS/VCFS findings, and fluorescence in situ hybridization (FISH)-confirmed microdeletion at chromosome 22q11.2. FISH diagnosis was perinatal in six patients but at 2 years of age in one child. Sclerocornea was bilateral in five patients. Findings included descemetocele (five eyes), microophthalmos (one eye), iridocorneal adhesions (one bilateral case), and severe anterior segment dysgenesis (one eye). Two patients underwent bilateral corneal transplantation; another two were scheduled for possible unilateral transplant. Sclerocornea is a static congenital condition in which the cornea is opaque and vascularized and resembles the sclera. The novel finding of sclerocornea suggests that a genetic locus at 22q11.2 may be involved in anterior segment embryogenesis. In most of our patients, the diagnostic process was underway, but in one patient 22q11.2 deletion was not suspected until after the child had already been undergoing treatment for sclerocornea for 2 years. Sclerocornea should be added to the clinical manifestations of the 22q11.2 deletion syndrome. Ophthalmologists diagnosing sclerocornea in children with systemic findings suggestive of 22q11.2 deletion should ensure appropriate genetic referral.

Peripheral Avascular Retina in a Term Male Neonate With Microvillus Inclusion Disease and Pancreatic Insufficiency.

The authors present the first case of peripheral avascular retina in a term male neonate with pancreatic exocrine insufficiency, atypical microvillus inclusion disease, flat tympanograms, and recurrent urinary tract infections. Clinical examination showed avascular peripheral retina to posterior zone II temporally, with a flat stage 1-like demarcation line, and no plus disease. Genetic testing results were normal. The patient developed peripheral neovascularization and underwent panretinal photocoagulation. This case likely represents mild Norrie disease, familial exudative vitreoretinopathy, or incontinentia pigmenti due to a Wnt signaling abnormality. While these conditions are usually more severe, a variable spectrum of Wnt abnormalities exists throughout the body.

Rectus muscle orbital wall fixation: a reversible profound weakening procedure.

INTRODUCTION: Surgical treatment of third nerve palsy, sensory exotropia and strabismus secondary to anomalous innervation of the rectus muscles, frequently require large rectus muscle recessions in an attempt to maintain alignment in the primary position and reduce the effects of misinnervation. The aim of this study was to describe and evaluate the results of inactivation of a rectus muscle by its attachment to the adjacent orbital wall. METHODS: Seven subjects diagnosed with third-nerve palsy (three cases), Duane syndrome (two cases), sensory exotropia (one case), and congenital aberrant innervation of vertical rectus muscles (one case) underwent rectus muscle inactivation by orbital wall fixation. The rectus muscle was disinserted from the globe and reattached to the adjacent orbital periosteum using non-absorbable sutures. This surgery was performed on the lateral rectus muscle in six subjects, and surgery was performed on both ipsilateral vertical rectus muscles in one. RESULTS: Postoperatively four of six patients were aligned within 12 prism diopters of orthotropia in primary position. All patients had improvement of the anomalous head posture. In Duane syndrome, lateral rectus inactivation markedly reduced co-contraction and globe retraction. No overcorrections resulted. CONCLUSION: A rectus muscle may be functionally inactivated when its insertion is attached to the orbital periosteum. Advantages of this procedure over extirpation and free tenotomy include permanent disinsertion of the muscle from globe and reversibility.

Surgical management of severe cocontraction, globe retraction, and pseudo-ptosis in Duane syndrome.

BACKGROUND: Correction of severe cocontraction and pseudo-ptosis present unique surgical challenges in patients with Duane syndrome. METHODS: We report four Duane syndrome patients with esotropia in primary position, poor abduction, and severe cocontraction causing limitation to adduction, globe retraction, and pseudo-ptosis. All were treated with partial tendon transposition of the vertical rectus muscles augmented with Foster fixation sutures and surgical weakening of the ipsilateral lateral rectus muscle. One patient had a large recession of the lateral rectus muscle, and in three patients, the lateral rectus muscle was inactivated by removing from the globe and attaching its insertion to the lateral orbital wall. RESULTS: Postoperatively, all patients were aligned within eight prisms diopters of orthotropia, had no face turn, and improved adduction and abduction. The two patients who had restriction to abduction on intraoperative forced ductions also had residual esotropia in primary position and underwent recession of the ipsilateral medial rectus muscle as a second procedure. Postoperative binocular single visual field was enlarged by 56 to 500% in the three patients who were tested preoperatively and postoperatively. Globe retraction and cocontraction were markedly relieved. Palpebral fissure widened 1.0 and 6.0 mm in two patients who had preoperative and postoperative measurements. CONCLUSION: In Duane syndrome patients, severe cocontraction, globe retraction, and limitation to adduction may improve if the lateral rectus muscle is maximally recessed or its insertion is inactivated from the globe. Partial transposition of the vertical rectus muscles augmented with Foster sutures improved the angle of esotropia in primary position and abduction. Medial rectus muscle recession is indicated when the passive forced duction test reveals moderate-to-severe restriction to abduction.

Partial rectus muscle-augmented transpositions in abduction deficiency.

PURPOSE: Lateral posterior fixation sutures increase the effect of full rectus extraocular muscle transpositions. Partial rectus muscle transposition may be indicated to minimize the risk of anterior ischemia when multiple rectus muscles require surgery to achieve ocular alignment. PURPOSE: To report a modification of full vertical rectus muscle transposition with lateral posterior fixation sutures for use in patients at risk for anterior segment ischemia. METHODS: Ten cases of unilateral split rectus muscle transposition augmented with lateral posterior fixation sutures were analyzed. Five patients had Duane's syndrome with esotropia in primary position, and five patients had sixth-nerve palsy. RESULTS: Seven patients had a history of ipsilateral rectus muscle surgery, and three patients underwent simultaneous surgery on ipsilateral horizontal rectus muscles. In Duane's syndrome patients, the preoperative angle of deviation at distance was 15.8 +/- 5.8 prism diopters (PD) (range, 10 to 25) compared with 3.2 +/- 4.4 PD (range, 0 to 8) postoperatively (P =.005). In patients with sixth-nerve palsy, the preoperative angle of deviation at distance was 45.2 +/- 23.9 PD (range, 16 to 80) compared with -5 +/- 14.1 PD (range, -30 to 5) postoperatively (P =.004). Postoperative binocular single visual fields enlarged in seven of seven patients. CONCLUSION: Partial rectus muscle-augmented transposition allows surgery on multiple ipsilateral rectus muscles in (1) Duane's syndrome patients with esotropia, marked cocontraction, and/or limitation to both horizontal rotations and in (2) sixth-nerve palsy patients with ipsilateral medial rectus tightness. Augmented partial rectus muscle transpositions improve ocular alignment and may enlarge binocular single fields in patients with persistent deviations despite previous muscle surgery.

Ocular involvement as the initial manifestation of Wegener's granulomatosis in children.

Ophthalmic manifestations are noted in about 50% of adults with Wegener's granulomatosis. Wegener's granulomatosis is a rare disease in the pediatric age group. The disease may present initially with ocular manifestations. We report the largest series to date of children whose ocular findings were the initial presenting signs of Wegener's granulomatosis.