Introduction< /p>
Rare diseases, also known as orphan diseases, are relatively small in number. Different regions have different definitions of rare diseases. In my country, rare diseases refer to diseases whose prevalence is less than 1/500,000 in the population or less than 1/10,000 in newborns.
It is estimated that there are about 16.8 million rare disease patients in my country. 5 rare diseases of the
I. Hepatolenticular degeneration
Liver Lenticular degeneration, also known as Wilson disease (WD), is an autosomal recessive disorder. Mutations in the ATP7B gene lead to obstacles in the transport and excretion of copper ions in the body, and copper accumulates in the liver, nervous system, cornea, kidneys and other organs, resulting in a series of clinical manifestations.
WD mainly occurs in children and adolescents and can affect multiple organs throughout the body. hepatic involvement is the first symptom in children, and nervous system involvement is the first symptom in adolescents and adults more. Liver disease can manifest as asymptomatic persistent elevation of transaminases, chronic hepatitis, cirrhosis, and acute liver failure. Nervous system involvement can be manifested as motor dysfunction, tremor, ataxia, etc., and some patients are combined with abnormal mental behavior. Other systems involved include the kidneys, blood system, bone and joints, heart, endocrine and reproductive systems.
Flowchart 1 WD Treatment
Second, hereditary hemochromatosis
hereditary Hemochromatosis (HH) is an autosomal recessive genetic disease, more common in males, caused by congenital excess iron deposition in liver cells, pancreatic epithelial cells, cardiomyocytes, joint soft tissue cells, etc., causing corresponding organ damage .
HH firstly involves the liver, which is mainly manifested as “black liver sign” on MRI. Then it involves the pancreas, then the myocardium, and finally the joints, resulting in multiorgan complications such as the heart, liver, pancreas, thyroid, gonads, skin and joints, including skin pigmentation, hepatomegaly and cirrhosis, diabetes, hyposexuality and testicular atrophy, thyroid Decreased function, joint disease, etc.
Treatment for PFIC includes symptomatic treatment (vitamins, medium-chain triglycerides, etc., to improve nutritional status), drug treatment [ursodeoxycholic acid 10-30 mg/(kg d)], surgical treatment (bile diversion), and liver transplantation.
4. Congenital disorders of bile acid synthesis
Inborn errors of bile acid synthesis (IEBAS) are congenital disorders of bile acid synthesis due to genetic defects in the enzymes necessary for the synthesis of the two major bile acids. IEBAS is a class of autosomal recessive genetic diseases.
The clinical manifestations of IEBAS are progressive cholestatic liver disease, neurological disease and malabsorption of fat-soluble vitamins. Diagnostics Comprehensive clinical symptoms, laboratory tests (increased conjugated bilirubin, elevated transaminase, normal gamma glutamate transpeptidase), auxiliary examinations and pathological biopsy are required, and the diagnosis depends on the detection of urinary bile acids and genetic testing.
treatment for IEBAS if severe hepatic impairment has occurred at the time of diagnosis If there is no serious liver function damage, follow the principle of individualized treatment, supplement primary bile acid, judge the curative effect and adjust the treatment according to the abnormal metabolite content in urine.
V. Homozygous familial hypercholesterolemia
< span>Familial hypercholesterolemia (FH) is a genetic disorder caused by mutations in one of the key genes of low-density lipoprotein cholesterol (LDL-C) catabolism. Homozygous familial hypercholesterolemia (HoFH) is caused by homozygous or compound heterozygous mutations in these key genes.
Main clinical manifestations of HoFH include significant LDL-C levels found immediately after birth Elevated, cholesterol deposits in the skin, eyes, and tendons to form xanthomas and fatty corneal arches.
The diagnosis of HoFH is based on genetic and clinical criteria.
Gene diagnostic criteria: LDLR, APOB, PCSK9 or LDLRAP1 are found in two alleles by genetic testing Mutations at genetic loci.
Clinical diagnostic criteria: LDL-C >500 mg/dl (>13 mmol/L) in the untreated case or after treatment LDL-C > 300 mg/dl (> 8 mmol/L) and one of the following: skin or tendon xanthoma before age 10; elevated parental LDL-C levels, meeting the criteria for heterozygous FH.
HoFH’s treatment includes a healthy lifestyle (A low saturated fat, low cholesterol, heart-healthy diet is recommended), medications (primarily statins, may be used in combination with other cholesterol-lowering medications), lipoprotein plasma clearance, liver transplantation, and other surgical treatments.
References:
< p>[1] Lv T, Jia J. Rare liver diseases are not rare in China[J]. Liver Int. 2022 Apr 1. doi: 10.1111/liv.15267.
< p>[2] Guidelines for the diagnosis and treatment of rare diseases (2019 edition).
[3] Xu Wenjiao, Li Changping, Shi Lei. Clinical features, diagnosis and treatment progress of hemochromatosis [J]. Modern Clinical Medicine, 2019,45(04):303-306.
[4] Jin Jinglan, Zhao Xu, Li Guangming, et al. American Society of Hepatology Blood Color Key points of guidelines for diagnosis and treatment of diseases[J]. Journal of Clinical Hepatobiliary Diseases, 2013,29(05):403-405.