Treatment Outcomes for Maple Syrup Urine Disease Detected by Newborn Screening.

OBJECTIVE: Maple syrup urine disease (MSUD), a life-threatening metabolic disorder, is included in newborn screening (NBS) programs worldwide. The study aims to evaluate the impact of NBS on the long-term outcome of MSUD patients. METHODS: We performed a prospective, national, multicenter, observational study. RESULTS: In the studied NBS cohort (N = 33; 22 classic MSUD [cMSUD], 11 variant MSUD [vMSUD]; median age at last visit 10.4 years), 32 (97%) patients survived, 58% of them had normal cognitive functions (median IQ 87). Initial peak leucine increased linearly with age in cMSUD (median: 1712 µmol/L), but not in vMSUD. Global IQ correlated inversely with the initial peak leucine concentration (P = .04; ß = -0.0081) and the frequency of decompensations (P = .02; ß = -9.133). A cluster analysis identified 2 subgroups differing in their long-term metabolic control (median leucine concentration: 162 vs 278 µmol/L; P < .001). In cMSUD, lower leucine concentrations were associated with a higher IQ (95.5 vs 80; P = .008). Liver transplantation (median age 5.8 years) was not associated with better cognitive outcome. NBS is highly sensitive for cMSUD, but vMSUD might be missed (N = 2 missed by NBS). CONCLUSIONS: NBS and the early start of treatment improve survival and long-term outcome in individuals with cMSUD. Disease severity is an important modifier of outcome; however, the time to NBS report and the quality of long-term metabolic control had an independent impact on cognitive outcome, highlighting the importance of an early diagnosis and the quality of treatment.

Novel VPS33B mutation in a patient with autosomal recessive keratoderma-ichthyosis-deafness syndrome.

Autosomal recessive keratoderma-ichthyosis-deafness (ARKID) syndrome is a rare multisystem disorder caused by biallelic mutations in VPS33B; only three patients have been reported to date. ARKID syndrome is allelic to arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome (MIM #208085), a severe disorder with early lethality whose phenotypic characteristics also include ichthyosis, hearing loss, severe failure to thrive, platelet dysfunction and osteopenia. We report on an 11-year-old male patient with ARKID syndrome and compound heterozygous VPS33B mutations, one of which [c.1440delG; p.(Arg481Glyfs*11)] was novel. Clinical features of this patient included ichthyosis, palmoplantar keratosis, hearing loss, intellectual disability, unilateral hip dislocation, microcephaly and short stature. He also had copper hepatopathy and exocrine pancreatic insufficiency, features that have so far been associated with neither ARKID nor ARC syndrome. The patient broadens the clinical and molecular spectrum of ARKID syndrome and contributes to genotype-phenotype associations of this rare disorder.

Severe allergic reactions to para-phenylenediamine in children and adolescents: should the patch test concentration of PPD be changed?

BACKGROUND: Semipermanent henna tattoos containing para-phenylenediamine (PPD) are a well-known cause of severe contact dermatitis, mainly in children. Another relevant exposure source to PPD are hair dyes, which are increasingly used by children and have also been reported to cause intense facial and scalp dermatitis. German patch test guidelines for children recommend that PPD should only be tested in patients who have had a henna tattoo, and then at a reduced concentration of PPD 0.5 % for 24 hours. PATIENTS AND METHODS: We report on patch test results in four patients, three children and one adolescent, with a history of contact dermatitis to henna tattoos or hair dye. We used the recommended or even lower patch test concentrations of PPD with 24-hours exposure in all patients. RESULTS AND CONCLUSION: All patients showed very strong patch test reactions to PPD and cross-reactions to related compounds even after dilution of PPD to as low as 0.05 %. Therefore, we suggest that in children with a history of allergic reactions to this compound, a titration test should be performed beginning at a concentration of maximal 0.05 %. This procedure has also been proposed previously based on a larger cases series in adults.

The floating Meckel.

A 10-year-old girl was hospitalized because of abdominal pain and significant gastrointestinal bleeding for 3 days with hematocrit of 28% and hemoglobin of 6.1 mmol/L. Gastroscopy and abdominal ultrasound did not reveal any gastrointestinal abnormalities and parameters of coagulation were normal. Because a Meckel diverticulum is one of the most common causes of lower gastrointestinal bleeding in children, a Tc-99m pertechnetate scan (Meckel's scan) was performed to identify ectopic gastric mucosa. Normally, a Meckel diverticulum is found in the right lower quadrant.