Fatty acid oxidation disorders: case series of a tertiary teaching hospital of Southern Brazil

Ida Vanessa Doederlein Schwartz 1,2; Bibiana Mello de Oliveira 2; Ana Paula Kurz de Boer2; Renata Barreto Tenorio2; Ana Karolina Maia de Andrade2; Carolina Fischinger Moura de Souza2

 

  1. Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
  2. Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil

Mitochondrial fatty acid β-oxidation disorders (FAOD) are a heterogeneous group of defects in fatty acid transport chain and mitochondrial β-oxidation, affecting energy homeostasis mainly in the liver, heart and skeletal muscles and often present with multi-system involvement, including several life-threatening manifestations. FAOD are inherited as autosomal recessive disorders and have a widely varied presentation, with either neonatal or late onset. In south Brazil, there are no studies on the clinical characteristics of FAOD patients until today.

Objective: To describe the main clinical and demographic features from a series of patients with FAOD managed at an outpatient referral clinic of these inborn errors of metabolism in a tertiary teaching Hospital of Southern Brazil.

Method: This is a retrospective study of FAOD patients followed at an outpatient clinic for treatment of inborn errors of metabolism in Medical Genetics service of Hospital de Clínicas, Porto Alegre, Brazil. Based on a convenience sample, we analyzed demographic and clinical data of eight patients with clinical, biochemical and/or molecular diagnosis of FAOD who are regularly seen at our outpatient unit.

Results: The diagnosis were Very long chain acyl-coA dehydrogenase deficiency (n=1); Long chain acyl-coA dehydrogenase deficiency (n=2); Multiple acyl-coA dehydrogenase deficiency (n=2); Carnitine palmitoyltransferase II deficiency (n=2) and Carnitine palmitoyltransferase II deficiency (n=1). The group comprised five women and four men, with ages ranging from three months to 39 years (median: 10 years; average: 11,07 years) and disease onset between 18 hours of life and 14 years old (median: 1 month; average: 22,12 months). Median age at diagnosis was 8 months (range: 20 days to 36 years of age). The diagnosis was confirmed by molecular tests in five patients. All patients had nonspecific presenting symptoms: seven out of the eight patients had hypoglycemia reported as the initial symptoms began. Seven had neurological symptoms which included seizure (n=3), developmental delay (n=1), hypotonia (n=6) and feeding difficulties (n=1).

Mitochondrial fatty acid β-oxidation disorders (FAOD) are a heterogeneous group of defects in fatty acid transport chain and mitochondrial β-oxidation, affecting energy homeostasis mainly in the liver, heart and skeletal muscles and often present with multi-system involvement, including several life-threatening manifestations. FAOD are inherited as autosomal recessive disorders and have a widely varied presentation, with either neonatal or late onset. In south Brazil, there are no studies on the clinical characteristics of FAOD patients until today.

Objective: To describe the main clinical and demographic features from a series of patients with FAOD managed at an outpatient referral clinic of these inborn errors of metabolism in a tertiary teaching Hospital of Southern Brazil.

Method: This is a retrospective study of FAOD patients followed at an outpatient clinic for treatment of inborn errors of metabolism in Medical Genetics service of Hospital de Clínicas, Porto Alegre, Brazil. Based on a convenience sample, we analyzed demographic and clinical data of eight patients with clinical, biochemical and/or molecular diagnosis of FAOD who are regularly seen at our outpatient unit.

Results: The diagnosis were Very long chain acyl-coA dehydrogenase deficiency (n=1); Long chain acyl-coA dehydrogenase deficiency (n=2); Multiple acyl-coA dehydrogenase deficiency (n=2); Carnitine palmitoyltransferase II deficiency (n=2) and Carnitine palmitoyltransferase II deficiency (n=1). The group comprised five women and four men, with ages ranging from three months to 39 years (median: 10 years; average: 11,07 years) and disease onset between 18 hours of life and 14 years old (median: 1 month; average: 22,12 months). Median age at diagnosis was 8 months (range: 20 days to 36 years of age). The diagnosis was confirmed by molecular tests in five patients. All patients had nonspecific presenting symptoms: seven out of the eight patients had hypoglycemia reported as the initial symptoms began. Seven had neurological symptoms which included seizure (n=3), developmental delay (n=1), hypotonia (n=6) and feeding difficulties (n=1).

Three patients had hepatomegaly and one had dehydration. The patient diagnosed at age 36 presented initially with lower limb weakness and pain, rhabdomyolysis, hypoglycemia and deep vein thrombosis. The patient with the earlier age of onset (18 hours) had hypotonia, feeding difficulties and hypothermia. Of these 8 patients, one had cardiomyopathy and arrhythmia. Unspecific dysmorphism was present in 4 patients. Two patients have a global developmental delay and one has a psychodiagnosis of moderate intellectual disability. Three patients had a previous sibling with unexplained death and one had consanguineous parents.

Conclusion: Throughout this descriptive study, we can emphasize the multisystemic, severe and life-threatening character of FAOD. Therefore, this group of pathologies requires integrated and multidisciplinary management. Although it is the most prevalent disorder in other series, no case of Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency was observed in this sample. We do not have newborn screening for such diseases at the national level, thus some patients arrive late to the reference centers for diagnosis and management. Greater awareness of this disorder among clinicians and pediatricians should aid their search for an etiological diagnosis in cases of severe hypoglycemia, hypotonia, hepatic and cardiac manifestations that might otherwise be improperly managed. Adequately treated patients can lead intellectually and socially satisfying lives with no severe limitations. Larger studies should be done to better understand those symptoms in Brazilian patients, as well as unified ones in a national basis.

Corresponding Author contact information (e-mail: ischwartz@hcpa.edu.br
phone: +55 51 3359 8011)

Three patients had hepatomegaly and one had dehydration. The patient diagnosed at age 36 presented initially with lower limb weakness and pain, rhabdomyolysis, hypoglycemia and deep vein thrombosis. The patient with the earlier age of onset (18 hours) had hypotonia, feeding difficulties and hypothermia. Of these 8 patients, one had cardiomyopathy and arrhythmia. Unspecific dysmorphism was present in 4 patients. Two patients have a global developmental delay and one has a psychodiagnosis of moderate intellectual disability. Three patients had a previous sibling with unexplained death and one had consanguineous parents.

Conclusion: Throughout this descriptive study, we can emphasize the multisystemic, severe and life-threatening character of FAOD. Therefore, this group of pathologies requires integrated and multidisciplinary management. Although it is the most prevalent disorder in other series, no case of Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency was observed in this sample. We do not have newborn screening for such diseases at the national level, thus some patients arrive late to the reference centers for diagnosis and management. Greater awareness of this disorder among clinicians and pediatricians should aid their search for an etiological diagnosis in cases of severe hypoglycemia, hypotonia, hepatic and cardiac manifestations that might otherwise be improperly managed. Adequately treated patients can lead intellectually and socially satisfying lives with no severe limitations. Larger studies should be done to better understand those symptoms in Brazilian patients, as well as unified ones in a national basis.

Corresponding Author contact information (e-mail: ischwartz@hcpa.edu.br
phone: +55 51 3359 8011)

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