Hepatic presentations of mitochondrial DNA depletion syndrome in children: A single tertiary liver centre experience.

Mitochondrial DNA depletion syndromes (MDDS) are a heterogeneous group and the hepato-cerebral phenotype is highly variable. A single centre retrospective study of all patients with MDDS presenting between January 2002 and September 2019. In total, 24 (13 male) children were identified: 7 POLG, 7 DGUOK, and 10 MPV17. Median age at presentation was 3 months (0.06-189). Sixteen had acute liver failure (ALF) and eight chronic cholestasis and/or raised transaminases. Four POLG patients developed liver injury after starting sodium valproate; Six DGUOK patients had neonatal ALF (median age 12 days), liver involvement developed at a median age of 2.5 and 11 months with MPV17 and POLG patients, respectively. Eighteen patients showed neurological involvement. Liver histology from 10 patients showed variable degrees of necrosis, steatosis, cholestasis, and fibrosis. Mitochondrial respiratory chain enzymology was abnormal in 5. Seventeen patients died at a median age of 8 months (range, 1-312) after a median time of 5.6 months from presentation: 5/7 POLG at 53 months, 7/7 DGUOK at 8 months and 5/10 MPV17 at 8 months. Three patients with MPV17 mutations received liver transplant (LT) at a median age of 24 months (range 5-132): all alive at 19, 18 and 3 years post-LT. Mutations in DGUOK and MPV17 genes are associated with a severe clinical phenotype characterised by early-onset/neonatal ALF or rapidly progressive cholestasis and death before 12 months of age. A subset of MPV17 patients was amenable to LT. Consideration for LT in infantile ALF remains difficult and rapid genetic testing is advised.

The natural history of classic galactosemia: lessons from the GalNet registry.

BACKGROUND: Classic galactosemia is a rare inborn error of carbohydrate metabolism, caused by a severe deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT). A galactose-restricted diet has proven to be very effective to treat the neonatal life-threatening manifestations and has been the cornerstone of treatment for this severe disease. However, burdensome complications occur despite a lifelong diet. For rare diseases, a patient disease specific registry is fundamental to monitor the lifespan pathology and to evaluate the safety and efficacy of potential therapies. In 2014, the international Galactosemias Network (GalNet) developed a web-based patient registry for this disease, the GalNet Registry. The aim was to delineate the natural history of classic galactosemia based on a large dataset of patients. METHODS: Observational data derived from 15 countries and 32 centers including 509 patients were acquired between December 2014 and July 2018. RESULTS: Most affected patients experienced neonatal manifestations (79.8%) and despite following a diet developed brain impairments (85.0%), primary ovarian insufficiency (79.7%) and a diminished bone mineral density (26.5%). Newborn screening, age at onset of dietary treatment, strictness of the galactose-restricted diet, p.Gln188Arg mutation and GALT enzyme activity influenced the clinical picture. Detection by newborn screening and commencement of diet in the first week of life were associated with a more favorable outcome. A homozygous p.Gln188Arg mutation, GALT enzyme activity of ≤ 1% and strict galactose restriction were associated with a less favorable outcome. CONCLUSION: This study describes the natural history of classic galactosemia based on the hitherto largest data set.

[Integrated treatment of cleft lip and palate. Organization of a treatment team]. / Tratamiento integral de las fisuras labio palatinas. Organización de un equipo de tratamiento.

OBJECTIVE: Collect the team experience in the treatment of children with cleft lip and palate, indicating the evolution of the team composition, advantages and improvement aspects, trying to transmit the need of team treatment. METHOD: The Bilbao cleft palate team was created in 1983, since then a cleft palate clinic, a parents group and a unit of velopharyngeal function has been developed. At present the team is composed by: pediatric reconstructor surgeon, speech therapist, orthodontist, dentist, pediatrician, ENT, maxillofacial surgeon, dismorphologyst, geneticist, nursing. RESULTS: One of the achievements has been the data unification, obtaining speech cephalometrics, photographic dental casts and video images with prospective view. At this time 403 cleft lip and palate children have been intervened, being essential the transdisciplinar team approach between surgeon, speech therapist and orthodontist. The importance of the team coordinator is pointed. The results of an audit of the two stage cleft palate closure in complete unilateral cleft lip and palate have obligated us to vary our surgical policy. The unresolved aspects are the lack of multidisciplinary team recognition at official level and the non existence of orthodontist in staff, without cost coverage of this treatment by public health system. CONCLUSIONS: In our experience the team treatment of cleft lip and palate has resulted in improvement of the clinic results, treatment protocols and training.

[Section of the sublingual frenulum. Are the indications correct?]. / Sección del frenillo sublingual. Son las indicaciones correctas?

OBJECTIVE: To see the relationship of the lingual frenum with speech and other oral functions, evaluating the surgical indications and the results of frenectomy. MATERIAL AND METHODS: In 1997 we operated 72 children with sublingual frenulum, a telephone questionnaire to the mothers of these patients was done, obtaining data about: age at surgery, professional reasons for referral, preoperative findings, pre-post operative speech therapy, place of surgery and type of anesthesia and mother's impression about the final result. RESULTS: Fifty valid questionnaires were obtained, the mean age at frenectomy was 3.03 years, 38% of children were sent due to speech problems, 60% due to some degree of tongue-tie and 2% due to dentofacial developmental anomalies. In 70% the patients were sent by a pediatrician and in 14% by a speech therapist. In 20% preoperative speech therapy was done and postoperatively in 30%. In 48% of cases, aged less than 2 years, speech was not possible to be evaluated. In the 11 cases with questionable results, a multidisciplinary reevaluation showed 7 cases with lingual dysfunction and poor tongue control, 4 cases with deglutitory anomalies and 3 cases with orofacial occlusal problems secondary to lingual dysfunction or altered oral habits. CONCLUSIONS: The presence of a nondisturbing lingual frenulum does not justify its surgical section, the frenectomy is indicated only in presence of altered oro-lingual functions caused by the tongue-tie such as: speech problems, errors of bite and deglutition, lingual dysfunction and anomalous oral habits.

Measurement of parathyrin in blood from thyroid veins: two radioimmunoassays compared in patients with primary hyperparathyroidism.

We measured parathyrin (PTH) in peripheral venous blood samples and in thyroid veins (both homolateral and contralateral to the lesion) in 13 patients with surgically confirmed parathyroid adenomas. Two different RIAs were used, one specific to the mid-region of the molecule (44-68, M-PTH), the other specific to the carboxy-terminal region (65-84, C-PTH). With the M-PTH assay we established a statistically significant multiple correlation (P less than 0.05) between the PTH concentrations in blood from the peripheral and thyroid veins; no significant correlation was found when we used the C-PTH assay. Our results confirm the superiority of the M-PTH RIA over the C-PTH RIA for study of hormonal secretion in primary hyperparathyroidism.