Case report of early biotinidase deficiency, a type of multiple carboxylase deficiency

Early biotinidase deficiency is an inherited form of multiple carboxylase deficiency leading to increased accumulation of biocytin and decreased biotin, predominantly effecting the central nervous system and skin. The symptoms can be reversed by early biotin supplementation.

Biotin Supplementation Creates the Misleading Diagnosis of Secondary Adrenal Insufficiency

Introduction: Biotin (vitamin B7) is a water-soluble vitamin and an essential cofactor for the metabolism of fatty acids, glucose, and amino acids. Cases of biotin interference with laboratory testing have been described, most of which involve interference with thyroid function tests. Interference with gonadal steroids, adrenal, and pituitary hormones are rare. We report a case of T3 thyrotoxicosis in which biotin supplementation created the appearance of secondary adrenal insufficiency (AI). Case: A 66-year-old woman was referred for the evaluation of low TSH. She had chronic fatigue, low libido, and dizziness on standing. Vitals were stable with BP 135/64 mmHg and BMI 23.5. No evidence of mucosal or cutaneous hyperpigmentation. Laboratory evaluation revealed low ACTH <5 (7.2–63.3 pg/mL), low morning cortisol 3.8 and high DHEA-S 174 (13–130 ug/dL). TSH was low at 0.32 (0.32–5.60 uIU/mL) with normal prolactin and appropriately elevated FSH and LH. The labs raised concern for secondary AI. Cosyntropin stimulation test (CST) was done with a peak cortisol of 17.4 ug/dL. In the setting of suppressed ACTH and failed CST, she was started on Hydrocortisone therapy. Subsequently, CT of abdomen was obtained due to high DHEA-S which showed normal appearance of both adrenals. Pituitary MRI was normal. A detailed review of the medication list revealed that the patient was taking a Biotin containing multivitamin. Repeat labs 1 week after stopping biotin showed normalization of ACTH 13.8 (7.2–63.3). Repeat CST showed a peak cortisol response of 24 ug/dL. Hydrocortisone was discontinued and the patient remained stable on subsequent follow-ups, without the need for further glucocorticoid replacement therapy. Thyroid lab abnormalities persisted after biotin cessation which led to the diagnosis of T3 thyrotoxicosis, the treatment of which caused resolution of the patient’s symptoms. Discussion: The recommended daily intake of biotin for adults is 30 µg/d. Many over-the-counter products, specifically those marketed for hair, skin, and nail growth, contain biotin 100-fold higher than the recommended intake. Biotin interference with competitive immunoassays can cause falsely elevated hormone levels, whereas biotin interference with immunometric “sandwich” assays falsely lowers hormone levels. In our case, low ACTH was clinically misleading, prompting numerous unnecessary radiographic and laboratory testing and treatment with hydrocortisone. The US Food and Drug Administration issued a safety communication regarding biotin interference with laboratory tests. Education and communication between laboratorians, providers, and patients play an important role in investigating potential lab interference and the need for alternative lab assays for an accurate diagnosis. Patients should be asked to stop taking biotin supplements for at least 48 hours prior to specimen collection if possible.

Rare Treatable Cause of Demyelinating Leukoencephalopathy That One Cannot Afford to Miss

Biotinidase deficiency is a treatable neurometabolic disorder. It usually presents during the first year of life with seizures, ataxia, hypotonia, vision and hearing disturbance, alopecia, and skin rashes. It can have various neuroimaging findings but demyelinating leukoencephalopathy is an unusual finding in children with biotinidase deficiency that can cause diagnostic challenge as it can radiologically mimic perinatal hypoxic–ischemic encephalopathy or other leukodystrophies. It reverses with early diagnosis and treatment with biotin supplementation and the outcome is rewarding.

Thiamine Treatment and Favorable Outcome in an Infant with Biallelic TPK1 Variants

Episodic encephalopathy due to mutations in the thiamine pyrophosphokinase 1 (TPK1) gene is a rare autosomal recessive metabolic disorder. Patients reported so far have onset in early childhood of acute encephalopathic episodes, which result in a progressive neurologic dysfunction including ataxia, dystonia, and spasticity. Here, we report the case of an infant with TPK1 deficiency (compound heterozygosity for two previously described pathogenic variants) presenting with two encephalopathic episodes and clinical stabilization under oral thiamine and biotin supplementation. In contrast to other reported cases, our patient showed an almost normal psychomotor development, which might be due to an early diagnosis and subsequent therapy.

Biotinidase deficiency

ObjectiveTo expand the genetic spectrum of hereditary spastic paraparesis by a treatable condition and to evaluate the therapeutic effects of biotin supplementation in an adult patient with biotinidase deficiency (BD).MethodsWe performed exome sequencing (ES) in a patient with the clinical diagnosis of complex hereditary spastic paraparesis. The patient was examined neurologically, including functional rating scales. We performed ophthalmologic examinations and metabolic testing.ResultsA 41-year-old patient presented with slowly progressive lower limb spasticity combined with optic atrophy. He was clinically diagnosed with complex hereditary spastic paraparesis. The initial panel diagnostics did not reveal the disease-causing variant; therefore, ES was performed. ES revealed biallelic pathogenic variants in the BTD gene leading to the genetic diagnosis of BD. BD is an autosomal recessive metabolic disorder causing a broad spectrum of neurologic symptoms, optic atrophy, and dermatologic abnormalities. When treatment is initiated in time, symptoms can be prevented or reversed by biotin supplementation. After diagnosis in our patient, biotin supplementation was started. One year after the onset of therapy, symptoms remained stable with slight improvement of sensory deficits.ConclusionsThese findings expand the genetic spectrum of the clinical diagnosis of complex hereditary spastic paraparesis by a treatable disease. Today, most children with BD should have been identified via newborn screening to start biotin supplementation before the onset of symptoms. However, adult patients and those born in countries without newborn screening programs for BD are at risk of being missed. Therapeutic success depends on early diagnosis and presymptomatic treatment.

Effects of Magnesium Biotinate Supplementation on Serum Insulin, Glucose, and Lipid Parameters Along with Gene Expressions of Intermediary Metabolism in Rats

Background: The objective of this work was to investigate the effects of a novel form of biotin (magnesium biotinate) at various levels on body weight, serum concentrations of glucose, insulin, cholesterol, and triglycerides, and liver expression of lipid metabolism-related genes such as SREBP-1c, FAS, AMPK-α1, ACC-1, ACC-2, PC, PCC and MCC in rats.Methods: A total of 42 male Sprague-Dawley rats were divided into six treatment groups and fed a standard diet-based egg white powdered diet supplemented with either commercial biotin (d-biotin) at 0.01, 1 or 100 mg/kg body weight or a novel form of biotin (magnesium biotinate) at 0.01, 1, or 100 mg/kg bodyweight for 35 days. The doses used at 0.01, 1 and 100 mg from each source represented a standard dietary dose (control), high dietary dose, and pharmacologic dose, respectively. Results: Bodyweight changes, feed intake, serum concentrations of glucose, insulin, creatine, and urea, and enzyme activities of ALT and AST were similar among treatments (P > 0.05). Serum total cholesterol and triglyceride concentrations of the rats decreased with biotin supplementation from both sources (P < 0.05). Concentrations were significantly lower with magnesium biotinate when comparing the 1 mg/kg dose groups (P < 0.05). Serum, liver, brain biotin concentrations, and liver cGMP contents were greater when rats were treated with magnesium biotinate versus d-biotin, particularly when comparing the 1 mg/kg and 100 mg/kg dose groups (P < 0.05). Both forms of biotin decreased the liver gene expression of SREBP‐1c and FAS and increased liver gene expression of AMPK-α1, ACC-1, ACC-2, PCC and MCC (P < 0.05). The magnitudes of responses were more emphasized with magnesium biotinate. Liver PC gene expression increased with biotin supplementation with no regard to dose or biotin form (P > 0.05).Conclusion: Results of the present work revealed that a new form of biotin, magnesium biotinate, compared with a commercial d-biotin, is more effective in reducing serum lipid concentrations and in regulating gene expressions of intermediary metabolism-related biomarkers.