Primary trimethylaminuria (fish odor syndrome) and hypothyroidism in an adolescent

Abstract

Primary trimethylaminuria (fish-odor syndrome) is a rare autosomal recessive inherited metabolic disorder due to decreased metabolism of trimethylamine by enzyme flavin-containing monooxygenase 3. We report an adolescent boy who was socially distressed with malodor and diagnosed trimethylaminuria by molecular analyses. The patient was previously found to have primary hypothyroidism at another center when he was being investigated for malodor. Our aim is to remind awareness of this rare, socially devastating metabolic disorder to physicians, especially family doctors and specialists such as pediatricians, adolescent doctors, psychiatrists and dermatologists. We also searched for a possible association between trimethylaminuria and hypothyroidism but didn't find out an exact pathophysiological link. Coexistence of primary trimethylaminuria and hypothyroidism might be coincidental. Key words: trimethylaminuria, fish odor syndrome, malodor, FMO3, hypothyroidism.Trimethylaminuria is a rare, socially debilitating metabolic disorder due to decreased metabolism of trimethylamine in liver by enzyme flavincontaining monooxygenase 3 (FMO3) secondary to FMO3 gene defect. 1-4 Affected patients have episodic or persistent unpleasant odor and also their breath, sweat, urine, saliva and other secretions smell characteristic of rotting fish. 5 Hypertension, migraine and other tyramine reactions are also described in these patients. 1,3 Psychiatric counseling is also important as it has strong psychosocial effects. We report one adolescent boy who was socially distressed with malodor and was diagnosed with primary trimethylaminuria. He was previously found to have hypothyroidism at another center when he was being investigated for malodor. We also analyzed if primary trimethylaminuria and primary hypothyroidism is associated or their coexistence is coincidental. Case ReportA twelve-year-old Turkish adolescent boy was admitted to hospital for the malodor of urine and sweat which had been noticed at six years of age. The complaint of patient was increasing by meat consumption. Urine and sweat was in normal color but smelled unpleasant. Parents had distant kinship. He was healthy and had normal diet. There was a history of levothyroxine treatment for hypothyroidism starting at six-years-old and varicocele operation at 11years of age. Hypothyroidism was diagnosed at another center when he was being investigated for malodor. At that time TSH level was 17 µIU/ ml (N: 0.6-5.5), free T4 level was 0.89 ng/dl (0.8-1.9) and levothyroxine 50 µg/day (2 µg/ kg/day) was started. His mother had a goiter and his sister also had hypothyroidism. Since the etiology of malodor was not detected, he was referred to our center. Physical examination findings were normal. Laboratory findings (total blood count, liver and kidney function tests, urine analyses and culture, tandem mass, urine organic acid, blood and urine quantitative amino acid analyses, biotinidase activity, homocysteine, lactate, pyruvate) were unremarkable except for the mild TSH elevati...

Variants of Flavin-Containing Monooxygenase 3 Found in Subjects in an Updated Database of Genome Resources

“…Moreover, four functionally known amino-acid-substituted FMO3 variants, namely FMO3 p.Ser195Leu, p.Arg223Gln, and p.Ile441Thr [found in Japanese families (Shimizu et al, 2021b)] and FMO3 p.Asn61Ser [reported in European families (Dolphin et al, 2000)] were also found in the updated 38K JPN database. Among the 24 already known amino-acid substituted FMO3 variants, FMO3 p.Ile37Thr (Teresa et al, 2006) and p.Arg387His (Kilic, 2017) have been reported in the literature, but their catalytic function remains unknown. Seventeen synonymous FMO3 variants were also detected in this study:…”